Cited by 839Advanced Sensor and Energy Harvesting MaterialsElectrochemical sensors and biosensorsAnalytical Chemistry and Sensors

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index; none of the 6 sources its claims cite is checked for support yet.

Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform

Open access
Emaminejad, Sam, Gao, Wei, Wu, Eric, Davies, Zoe A., Yin Yin Nyein, Hnin, Challa, Samyuktha, Ryan, Sean P., Fahad, Hossain M., Chen, Kevin, Shahpar, Ziba, Talebi, Salmonn, Milla, Carlos, Javey, Ali, Davis, Ronald W.·2017·Proceedings of the National Academy of Sciences

Abstract

Significance: The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. Through devising an electrochemically enhanced, programmable, and miniaturized iontophoresis interface, integrated in a wearable sensing platform, we demonstrated a method for periodic sweat extraction and in situ analysis. The system can be programmed to induce sweat with various secretion profiles, which in combination with the in situ analysis capability allow us to gain real-time insight into the sweat-secretion and gland physiology. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

The paper presents a fully integrated wearable platform that uses an electrochemically enhanced iontophoresis interface to extract sweat on demand and analyze Na⁺, Cl⁻, and glucose in situ. It demonstrates elevated sweat electrolytes in cystic fibrosis patients and a preliminary blood/sweat glucose correlation after oral glucose intake.

Key findings

  • In on-body testing, average sweat sodium and chloride levels at 25 min were 26.7 and 21.2 mM for six healthy subjects versus 82.3 and 95.7 mM for three CF patients, respectively; CF patients also showed lower sweat sodium than chloride, opposite to healthy subjects.
  • For glucose, seven healthy subjects before and after 30 g oral glucose showed similar sweat and blood glucose patterns, with increases in both sweat and blood in six out of seven fasting subjects.
  • The iontophoresis platform achieved sweat secretion rates above 100 nL/min/cm²; 10% acetylcholine produced a high short-lived rate of 354 nL/min/cm², while 10% methacholine gave rapid onset and sustained high secretion and was used for subsequent on-body experiments.
  • Sensor characterizations showed near-Nernstian Na⁺ and Cl⁻ sensitivities of 63.2 and 55.1 mV per decade, a glucose sensitivity of 2.1 nA/μM, and biosensor sensitivity variations of <5% over 2 wk.

Methods

  • The wearable system used a flexible PET electrode array with iontophoresis and sensing electrodes, agonist-loaded hydrogels, and a flexible printed circuit board built around an ATmega328P microcontroller with Bluetooth, programmable current delivery, and signal-conditioning circuits.
  • Human subject studies included six healthy volunteers and three CF patients for sweat electrolyte testing, and seven healthy subjects for fasting and post-30 g oral glucose trials; on-body work was IRB-approved at UC Berkeley and Stanford.
  • Sensor performance was characterized in 10–160 mM NaCl and 0–100 μM glucose solutions, and sweat-rate profiles were characterized using three cholinergic agonist hydrogels at two concentrations with a commercial Q-sweat sensor.

Limitations

  • The paper states that the glucose work is preliminary, that the metabolic correlation between sweat and blood glucose has not been well studied, and that future work should integrate temperature, pH, and sweat-rate sensors to calibrate or normalize glucose measurements.
  • The paper also states that future efforts should include a wider panel of biomarkers and peripheral electrochemical/physical sensors for large-scale clinical and physiological investigations.
  • Evident from the text: the human studies are small (six healthy/three CF; seven glucose subjects), and no formal statistical comparisons or full correlation analyses are reported.

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Integrity signals

Registry

Crossref · 10.1073/pnas.1701740114

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

23 Own result · 11 No basis given · 10 Own interpretation · 6 Not checked yet · 6 Own method

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Show all 34 claims

  • It may state two separate claims as one. 15
  • Probably not a substantial claim. 7
22 of 22
  • The paper relies on this without support.

    Sweat is inaccessible in sedentary individuals in large volume (at least 10 μL) for on-demand and in situ analysis, limiting broad population monitoring.

    “The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 μL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information.”
  • The paper relies on this without support.

    The conventional iontophoresis procedure involves separate stimulation, collection, and analysis steps, requiring extensive manual sample handling and failing to provide real-time insight into the secretion process.

    “The conventional procedure involves stimulation, collection, and analysis all in separate steps, which not only requires extensive manual sample handling steps, but also fails to provide real-time insight into the secretion process.”
  • The paper relies on this without support.

    The metabolic correlation between sweat glucose and blood glucose has not been well studied.

    “Although there is literature reporting that sweat glucose level is related with blood glucose level (26), their metabolic correlation has not been well studied.”
  • The paper relies on this without support.

    The challenge remains in devising an iontophoresis interface that can extract sufficient sweat for robust sensing without electrode corrosion and burning or discomfort in subjects.

    “The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects.”
  • The paper relies on this without support.

    Elevated sweat sodium and chloride ion content is a diagnostic marker for cystic fibrosis.

    “To illustrate the value of our solution as a diagnostic tool, we used the platform to detect the elevated sweat sodium and chloride ions content in the CF patients.”
5 of 5

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Metadata

Authors
Emaminejad, S., Gao, W., Wu, E., Davies, Z. A., Yin Yin Nyein, H., Challa, S., Ryan, S. P., Fahad, H. M., Chen, K., Shahpar, Z., Talebi, S., Milla, C., Javey, A., & Davis, R. W.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • University of California, Berkeley (US)
  • Stanford Medicine (US)
  • Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720;
  • Stanford University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2017-04-17
Volume
114
Issue
18
Pages
4625-4630
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2607347870
Cited by
839
References
28
Citations by year
2026: 71 · 2025: 92 · 2024: 107 · 2023: 106 · 2022: 99 · 2021: 113 · 2020: 97 · 2019: 96 · 2018: 49 · 2017: 8
FWCI
30.79
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • National Institutes of Health (HG000205)
  • National Science Foundation (NASCENT)
  • U.S. Department of Energy (DE-AC02-05CH11231)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Advanced Sensor and Energy Harvesting Materials
  • Physical Sciences › Chemistry › Analytical Chemistry › Electrochemical sensors and biosensors
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Chemistry and Sensors
Keywords
sweat analysis, iontophoresis, wearable biosensors, cystic fibrosis, blood glucose monitoring, sweat electrolytes, non-invasive diagnosis, continuous health monitoring
MeSH terms
Wearable Electronic Devices, Cystic Fibrosis, Glucose, Humans, Iontophoresis, Monitoring, Physiologic, Sweat

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